Liver regeneration after living donor transplantation: adult-to-adult living donor liver transplantation cohort study

Abstract

Adult-to-adult living donors and recipients were studied to characterize patterns of liver growth and identify associated factors in a multicenter study. Three hundred and fifty donors and 353 recipients in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) receiving transplants between March 2003 and February 2010 were included. Potential predictors of 3-month liver volume included total and standard liver volumes (TLV and SLV), Model for End-Stage Liver Disease (MELD) score (in recipients), the remnant and graft size, remnant-to-donor and graft-to-recipient weight ratios (RDWR and GRWR), remnant/TLV, and graft/SLV. Among donors, 3-month absolute growth was 676 ± 251 g (mean ± SD), and percentage reconstitution was 80% ± 13%. Among recipients, GRWR was 1.3% ± 0.4% (8 < 0.8%). Graft weight was 60% ± 13% of SLV. Three-month absolute growth was 549 ± 267 g, and percentage reconstitution was 93% ± 18%. Predictors of greater 3-month liver volume included larger patient size (donors and recipients), larger graft volume (recipients), and larger TLV (donors). Donors with the smallest remnant/TLV ratios had larger than expected growth but also had higher postoperative bilirubin and international normalized ratio at 7 and 30 days. In a combined donor-recipient analysis, donors had smaller 3-month liver volumes than recipients adjusted for patient size, remnant or graft volume, and TLV or SLV (P = 0.004). Recipient graft failure in the first 90 days was predicted by poor graft function at day 7 (HR = 4.50, P = 0.001) but not by GRWR or graft fraction (P > 0.90 for each). Both donors and recipients had rapid yet incomplete restoration of tissue mass in the first 3 months, and this confirmed previous reports. Recipients achieved a greater percentage of expected total volume. Patient size and recipient graft volume significantly influenced 3-month volumes. Importantly, donor liver volume is a critical predictor of the rate of regeneration, and donor remnant fraction affects postresection function. Liver Transpl 21:79-88, 2015. © 2014 AASLD.

Figure 1

Study population and analysis subsets.

Figure 2

Box and whisker plot of liver volume before and after transplant. The bottom and top of boxes indicate the 25^th and 75^th percentile, middle line indicates the median, and + the mean. Whiskers extend up to 1.5 times the interquartile range (IQR) from the bottom and top edges of the box, ending at the last actual data point within the range.

Figure 3

(a) Donor and recipient absolute growth at 3 months by lobe. (b) Donor and recipient percent liver reconstitution at 3 months by lobe. Each regeneration measure is based on remnant lobe for donors and on transplanted lobe for recipients. The bottom and top of boxes indicate the 25^th and 75^th percentile respectively, middle line indicates the median, and + indicates the mean. Whiskers extend up to 1.5 times the interquartile range (IQR) from the bottom and top edges of the box, ending at the last actual data point within the range.

Figure 3

(a) Donor and recipient absolute growth at 3 months by lobe. (b) Donor and recipient percent liver reconstitution at 3 months by lobe. Each regeneration measure is based on remnant lobe for donors and on transplanted lobe for recipients. The bottom and top of boxes indicate the 25^th and 75^th percentile respectively, middle line indicates the median, and + indicates the mean. Whiskers extend up to 1.5 times the interquartile range (IQR) from the bottom and top edges of the box, ending at the last actual data point within the range.

Figure 4

Predicted donor liver volume at 3 months (Y axis) and remnant liver fraction (X axis) at transplantation based on donor model. Predicted values are shown for three hypothetical 78kg donors with TLV of 1300cc, 1550cc, and 1800cc.